Picture of Phil Cole

Philip A. Cole, M.D., Ph.D.

Professor of Medicine and Biological Chemistry and Molecular Pharmacology

Our research involves the chemical biology of protein post-translational modifcations (PTMs) in the context of signaling, epigenetics, and cancer.  We develop and apply chemical approaches including protein semisynthesis and small molecule probes to the study of protein phosphorylation, acetylation, ubiquitination, and other PTMs in enzymes and cellular networks. 

Phil Cole graduated from Yale University with a B.S. in Chemistry in 1984 and then spent a year as a Churchill Scholar at the University of Cambridge.  Cole went on to obtain M.D. and Ph.D. degrees from Johns Hopkins where he pursued research in bioorganic chemistry in 1991.  Cole then entered clinical and post-doctoral training at Brigham and Women's Hospital and Harvard Medical School prior to joining Rockefeller University in 1996 as a junior lab head.  In 1999, Cole returned to Johns Hopkins as professor and director of pharmacology where he served until 2017, when he moved to Harvard Medical School and Brigham and Women's Hospital as professor of medicine and biological chemistry and molecular pharmacology.  His research interests are in the area of chemical biology, protein post-translational modifications, cell signaling, and epigenetics.

Research:

Our research involves the chemical biology of protein post-translational modifcations (PTMs) in the context of signaling, epigenetics, and cancer.  We develop and apply chemical approaches including protein semisynthesis and small molecule probes to the study of protein phosphorylation, acetylation, ubiquitination, and other PTMs in enzymes and cellular networks.  We are currently investigating the functions, regulation, and mechanisms of PTEN lipid phosphatase, Akt protein kinase, NEDD4 ubiquitin ligases, LSD1 histone demethylase, HDAC1 deacetylase, the CoREST complex, and p300/CBP acetyltransferase.  We strive to translate our findings in signaling and epigenetics to identify novel therapeutic opportunities for the treatment of cancer and other diseases.

Address: 

New Research Building

77 Avenue Louis Pasteur

Room 168C

Boston, MA 02115

Publications View
Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors.
Authors: Authors: Kalin JH, Wu M, Gomez AV, Song Y, Das J, Hayward D, Adejola N, Wu M, Panova I, Chung HJ, Kim E, Roberts HJ, Roberts JM, Prusevich P, Jeliazkov JR, Roy Burman SS, Fairall L, Milano C, Eroglu A, Proby CM, Dinkova-Kostova AT, Hancock WW, Gray JJ, Bradner JE, Valente S, Mai A, Anders NM, Rudek MA, Hu Y, Ryu B, Schwabe JWR, Mattevi A, Alani RM, Cole PA.
Nat Commun
View full abstract on Pubmed
Protein Chemical Approaches to Understanding PTEN Lipid Phosphatase Regulation.
Authors: Authors: Dempsey DR, Cole PA.
Methods Enzymol
View full abstract on Pubmed
Assembly of PGAM5 into Multimeric Complexes Provides a Mechanism for Allosteric Regulation of Phosphatase Activity.
Authors: Authors: Tipton P, Su T, Hannink M.
Methods Enzymol
View full abstract on Pubmed
Measurement of nanoscale DNA translocation by uracil DNA glycosylase in human cells.
Authors: Authors: Esadze A, Rodriguez G, Weiser BP, Cole PA, Stivers JT.
Nucleic Acids Res
View full abstract on Pubmed
CBP Regulates Recruitment and Release of Promoter-Proximal RNA Polymerase II.
Authors: Authors: Boija A, Mahat DB, Zare A, Holmqvist PH, Philip P, Meyers DJ, Cole PA, Lis JT, Stenberg P, Mannervik M.
Mol Cell
View full abstract on Pubmed
Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours.
Authors: Authors: Lasko LM, Jakob CG, Edalji RP, Qiu W, Montgomery D, Digiammarino EL, Hansen TM, Risi RM, Frey R, Manaves V, Shaw B, Algire M, Hessler P, Lam LT, Uziel T, Faivre E, Ferguson D, Buchanan FG, Martin RL, Torrent M, Chiang GG, Karukurichi K, Langston JW, Weinert BT, Choudhary C, de Vries P, Van Drie JH, McElligott D, Kesicki E, Marmorstein R, Sun C, Cole PA, Rosenberg SH, Michaelides MR, Lai A, Bromberg KD.
Nature
View full abstract on Pubmed
Disordered N-Terminal Domain of Human Uracil DNA Glycosylase (hUNG2) Enhances DNA Translocation.
Authors: Authors: Rodriguez G, Esadze A, Weiser BP, Schonhoft JD, Cole PA, Stivers JT.
ACS Chem Biol
View full abstract on Pubmed
Allosteric regulation of epigenetic modifying enzymes.
Authors: Authors: Zucconi BE, Cole PA.
Curr Opin Chem Biol
View full abstract on Pubmed
Investigation of N-Terminal Phospho-Regulation of Uracil DNA Glycosylase Using Protein Semisynthesis.
Authors: Authors: Weiser BP, Stivers JT, Cole PA.
Biophys J
View full abstract on Pubmed
Endotoxemia-mediated activation of acetyltransferase P300 impairs insulin signaling in obesity.
Authors: Authors: Cao J, Peng J, An H, He Q, Boronina T, Guo S, White MF, Cole PA, He L.
Nat Commun
View full abstract on Pubmed